Use of stem cells for treatment of excessive inflammation

Abstract

Methods and compositions comprising ABCB5+ stem cell to treat hyper-inflammatory disorders, such as acute respiratory distress syndrome (ARDS) are provided. Such compositions may be used to treat, for example, patients with severe COVID19.

1 . A method of treating a hyper-inflammatory disorder in a human subject, the method comprising:
 administering to the subject a composition comprising ABCB5+ stem cells in an effective amount to treat the hyper-inflammatory disorder.   
     
     
         2 . The method of  claim 1 , wherein the dose is 1×10 6  to 1×10 10 , optionally 1×10 8  ABCB5+ stem cells. 
     
     
         3 . The method of  claim 1 , further comprising administering the dose to the subject two times. 
     
     
         4 . The method of any one of  claim 1 , wherein the dose is administered to the subject three times. 
     
     
         5 . The method of  claim 1 , wherein the dose is administered to the subject four times. 
     
     
         6 . The method of  claim 3 , wherein the doses are administered one day apart. 
     
     
         7 . The method of  claim 1 , wherein the composition comprises ABCB5+ stem cells and a pharmaceutically acceptable excipient. 
     
     
         8 . The method of  claim 7 , wherein the pharmaceutically acceptable excipient is human serum albumin/Ringer/glucose solution (HRG). 
     
     
         9 . The method of  claim 1 , wherein the inflammatory disorder is acute respiratory distress syndrome (ARDS). 
     
     
         10 . The method of  claim 1 , wherein the subject has a severe COVID-19 infection. 
     
     
         11 . The method of  claim 1 , wherein administration of the dose increases the level of IL-IRA, IL-10, or both, in the subject. 
     
     
         12 . The method of  claim 1 , wherein administration of the dose decreases the level of TNF-α, IL-1β, or both, in the subject. 
     
     
         13 . The method of  claim 1 , wherein administration of the dose promotes a switch from M1 macrophages to M2 macrophages. 
     
     
         14 . A method of treating a human subject having a SARS infection, the method comprising:
 administering a composition of ABCB5+ stem cells to the subject in an effective amount to treat the subject.   
     
     
         15 . The method of  claim 14 , wherein the SARS infection is a SARS-CoV-2 infection. 
     
     
         16 . The method of  claim 14 , wherein the ABCB5+ stem cells are dermal ABCB5+ stem cells. 
     
     
         17 . The method of  claim 14 , wherein the ABCB5+ stem cells are ocular ABCB5+ stem cells. 
     
     
         18 . The method of  claim 14 , wherein the ABCB5+ stem cells are a population of synthetic ABCB5+ stem cells. 
     
     
         19 . The method of  claim 18 , wherein greater than 99%, 99.5%, 99.7%, 99.9%, 99.99%, 99.998%, 99.999%, or 99.999997% of the population of synthetic ABCB5+ stem cells is an in vitro progeny of physiologically occurring skin-derived ABCB5-positive mesenchymal stem cells. 
     
     
         20 . The method of  claim 14 , wherein the cells are administered intravenously. 
     
     
         21 . The method of  claim 14 , wherein a dose of the cells is 1×10 6  to 1×10 10  ABCB5+ stem cells. 
     
     
         22 . The method of  claim 1 , wherein administration of the cells increases the level of IL-IRA, IL-10, or both, in the subject. 
     
     
         23 . The method of  claim 1 , wherein administration of the cells decreases the level of TNF-α, IL-1β, or both, in the subject. 
     
     
         24 . The method of  claim 1 , wherein administration of the cells promotes a switch from M1 macrophages to M2 macrophages.